1.Introduction:Nanoparticles in drug delivery
In recent years,signi ?cant efforts have been devoted to use the potentials of nanotechnology in drug delivery since it offers a suitable means of site-speci ?c and/or time-controlled delivery of small or large molecular weight drugs and other bioactive agents [1–9].Pharma-ceutical nanotechnology focuses on formulating therapeutically active agents in biocompatible nanoforms such as nanoparticles,nanocap-sules,micellar systems,and conjugates.These systems offer many advantages in drug delivery,mainly focusing on improved safety and ef ?cacy of the drugs, e.g.providing targeted delivery of drugs,improving bioavailability,extending drug or gene effect in target tissue,and improving the stability of therapeutic agents against chemical/enzymatic degradation [3].The nanoscale size of these delivery systems is the basis for all these advantages [10].
By a general de ?nition,nanoparticles vary in size from 10to 1000nm.The drug is dissolved,entrapped,encapsulated or attached to a nanoparticle matrix and depending upon the method of preparation,nanoparticles,nanospheres or nanocapsules can be obtained.Nanocapsules are vesicular systems in which the drug is con ?ned to a cavity surrounded by a boundary structure, e.g.,polymeric,while nanospheres are matrix spherical systems in which the drug is physically and uniformly dispersed [11](Fig.1).
Several types of nanoparticulate systems have been attempted as potential drug delivery systems,including biodegradable polymeric nanoparticles,polymeric micelles,solid nanoparticles,lipid-based nanoparticles, e.g.,Solid lipid nanoparticles (SLN),nanostructured lipid carriers (NLC)and lipid drug conjugate (LDC),nanoliposomes,inorganic nanoparticles,dendrimers,magnetic nanoparticles,Ferro-?uids,and quantum dots.2.Hydrogels:A brief overview
Originally,Wichterle and Lim [12]introduced a type of hydro-phobic gel for biological uses in the early ter on toward the present,a huge sum of efforts and studies has been devoted to advancing and extending the potentials attributed to hydrogels [13–21].Ever-growing hydrogel technology has led to dramatic advances in pharmaceutical and biomedical era [22–25].By de ?nition,hydro-gels are polymeric networks with three-dimensional con ?guration capable of imbibing high amounts of water or biological ?uids [26–28].Their af ?nity to absorb water is attributed to the presence of hydrophilic groups such as –OH,–CONH –,–CONH2–,and –SO3H in polymers forming hydrogel structures [29].Due to the contribution of these groups and domains in the network,the polymer is thus hydrated to different degrees (sometimes,more than 90%wt.),depending on the nature of the aqueous environment and polymer composition [30–33].In contrast,polymeric networks of hydrophobic
characteristics (e.g.,poly(lactic acid)(PLA)or poly(lactide-co-glyco-lide)(PLGA))have limited water absorbing capacities (b 5–10%).While the water content of a hydrogel determines its unique physicochem-ical characteristics,these structures have some common physical properties resembling that of the living tissues,than any other class of synthetic biomaterials,which is attributed to their high water content,their soft and robbery consistency,and low interfacial tension with water or biological ?uids [34,35].Despite their high water absorbing af ?nity,hydrogels show a swelling behavior instead of being dissolved in the aqueous surrounding environment as a consequence of the critical crosslinks present in the hydrogel structure.These crosslinks are from two main categories including:i)physical (entanglements or crystallites),and ii)chemical (tie-points and junctions)[36–41].The crosslinks in the polymer network are provided by covalent bonds,hydrogen binding,van der Waals interactions,or physical entangle-ments [42,43].
2.1.Hydrogel classi ?cations
To achieve a hydrogel system with predetermined and well-de ?ned physicochemical parameters and release pro ?les,a knowl-edge of polymer network synthesis and chemistry,quantitative and modelistic features of materials,interaction parameters,disintegra-tion/release kinetic,and transport phenomena seems to be playing fundamentally important roles.In a general view,hydrogels can be classi ?ed based on a variety of characteristics,including the nature of side groups (neutral or ionic),mechanical and structural features (af ?ne or phantom),method of preparation (homo-or co-polymer),physical structure (amorphous,semicrystalline,hydrogen bonded,supermolecular,and hydrocollodial),and responsiveness to physiolo-gic environment stimuli (pH,ionic strength,temperature,electro-magnetic radiation,etc.)[26,27,33,36–41,44–49].The polymers commonly used in preparation of hydrogels with pharmaceutical and biological applications are from natural or synthetic origins [23,49–53].Typical examples of natural,synthetic and combinational,i.e.,semisynthetic polymers used in hydrogel preparations are summarized in Table 1.Although hydrogels of natural origin may show mechanically sub-optimal characteristics and may exert im-munogenicity or evoke in ?ammatory responses due to the
presence
Fig.1.Schematic representation of a nanosphere (A)and a nanocapsules (B).In nanospheres,the whole particle consists of a continuous polymer network.Nanocap-sules present a core-shell structure with a liquid core surrounded by a polymer shell.
Table 1
Hydrophilic polymers used in preparation of hydrogels
Natural polymers and their derivatives
Anionic polymers :HA,alginic acid,pectin,carrageenan,chondroitin sulfate,dextran sulfate
Cationic polymers :chitosan,polylysine
Amphipathic polymers :collagen (and gelatin),carboxymethyl chitin,?brin Neutral polymers :dextran,agarose,pullulan
Synthetic polymers
Polyesters :PEG –PLA –PEG,PEG –PLGA –PEG,PEG –PCL –PEG,PLA –PEG –PLA,PHB,P(PF-co-EG)6acrylate end groups,P(PEG/PBO terephthalate)
Other polymers :PEG-bis-(PLA-acrylate),PEG6CDs,PEG-g-P(AAm-co-Vamine),PAAm,P (NIPAAm-co-AAc),P(NIPAAm-co-EMA),PVAc/PVA,PNVP,P(MMA-co-HEMA),P(AN-co-allyl sulfonate),P(biscarboxy-phenoxy-phosphazene),P(GEMA-sulfate)
Combinations of natural and synthetic polymers
P(PEG-co-peptides),alginate-g-(PEO –PPO –PEO),P(PLGA-co-serine),collagen-acrylate,alginate-acrylate,P(HPMA-g-peptide),P(HEMA/Matrigel®),HA-g-NIPAAm
Abbreviations :HA,hyaluronic acid;PEG,poly (ethylene glycol);PLA,poly(lactic acid);PLGA,poly(lactic-co-glycolic acid);PCL,polycaprolactone;PHB,poly(hydroxy butyrate);PF,propylene fumarate;EG,ethylene glycol;PBO,poly(butylene oxide);CD,cyclodextrin;PAAm,polyacrylamide PNIPAAm,poly(N -isopropyl acrylamide);PVA,poly(vinyl alcohol);PVamine,poly(vinyl amine)PVAc,poly(vinyl acetate);PNVP,poly (N -vinyl pyrrolidone);PAAc,poly(acrylic acid);HEMA,hydroxyethyl methacrylate;PAN,polyacrylonitrile;PGEMA,poly(glucosylethyl methacrylate);PEO,poly(ethylene oxide);PPO,poly(propyleneoxide);PHPMA,poly(hydroxypropyl methacrylamide);PEMA,poly (ethyl methacrylate);PAN,polyacrylonitrile;PMMA,poly(methyl methacrylate).
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M.Hamidi et al./Advanced Drug Delivery Reviews 60(2008)1638–1649